Position title: Assistant Professor (also Medicine)
Phone: (608) 262-8667
6206B Biochemical Sciences Building
440 Henry Mall, Madison, WI 53706
• B.S., M.Sc., Istanbul University, School of Pharmacy, 2001
• Ph.D., Baylor College of Medicine, 2007
• Postdoctoral Fellow, Harvard University, 2013
Honors & Awards
• Translational Basic & Clinical Pilot Award, Institute for Clinical and Translational Research, 2018
• Shaw Scientist Award, Greater Milwaukee Foundation, 2016
• Career Development Award, Juvenile Diabetes Research Foundation, 2014
• Research Scientist Development Award (KO1), National Institute of Health, 2014
• Young Investigator Award, American Society of Bone and Mineral Research, 2007
The endoplasmic reticulum (ER) is a dynamic organelle that plays a key role for cellular homeostasis, development, and stress responsiveness. In response to cellular stress induced by toxins, unfolded proteins and inflammation, a well-established signaling cascade, the unfolded protein response (UPR), is activated. During UPR, perturbations in ER homeostasis are sensed and transduced by ER membrane localized proteins to the cytoplasm and nucleus to initiate a compensatory response. While UPR plays a critical role for cell survival during acute stress conditions, hyperactivated UPR or unresolvable stress lead to cell demise. Thus, the unfolded protein response regulates both death and survival effectors. How or when these ER membrane proteins determine whether a cell will survive or die upon ER stress is currently unknown.
We recently showed that, the adaptive functions of the UPR were greatly reduced in β-cells of two different type 1 diabetes (T1D) mouse models and human patients during the progression of T1D. Diabetes incidence in these mouse models was dramatically reduced by mitigating β-cell ER stress with a chemical chaperone. These data suggest that the UPR plays a critical role in β-cell function and survival in T1D. Although this study provides the first direct link between the UPR and T1D pathogenesis and opens the door to a completely novel area of T1D biology, the β-cell specific function of the UPR sensors, their downstream targets, and the molecular mechanisms by which the UPR regulates pancreatic β-cell death/survival during T1D progression still remain largely unknown.
Our laboratory uses biochemistry, cell biology, genetics, -omics and immunology as well as sophisticated genetic and pharmacological tools to understand β-cell specific functions of the UPR sensors, their downstream targets and the molecular mechanisms by which the UPR regulates pancreatic β-cell death/survival.
Publications of Note
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•Differential Expression of Ormdl Genes in the Islets of Mice and Humans with Obesity
Hugo Lee, Rachel J Fenske, Tugce Akcan, Elliot Domask, Dawn B Davis, Michelle E Kimple, Feyza Engin
iScience. 2020 Jul 24;23(7):101324.doi: 10.1016/j.isci.2020.101324. Epub 2020 Jun 29.
•Beta Cell Dedifferentiation Induced by IRE1α Deletion Prevents Type 1 Diabetes
Hugo Lee, Yong-Syu Lee, Quincy Harenda, Stefan Pietrzak, Hülya Zeynep Oktay, Sierra Schreiber, Yian Liao, Shreyash Sonthalia, Ashley E Ciecko, Yi-Guang Chen, Sunduz Keles, Rupa Sridharan, Feyza Engin
Cell Metab. 2020 Apr 7;31(4):822-836.e5. doi: 10.1016/j.cmet.2020.03.002. Epub 2020 Mar 26.
•Restoration of the unfolded protein response in pancreatic β cells protects mice against type 1 diabetes
Feyza Engin, Alena Yermalovich, Truc Nguyen, Sarah, Wenxian Fu, Decio L Eizirik, Diane Mathis, Gökhan S Hotamisligil
Sci Transl Med. 2013 Nov 13;5(211):211ra156. doi: 10.1126/scitranslmed.3006534.
•Dimorphic effects of Notch signaling in bone homeostasis
Feyza Engin, Zhenqiang Yao, Tao Yang, Guang Zhou, Terry Bertin, Ming Ming Jiang, Yuqing Chen, Lisa Wang, Hui Zheng, Richard E Sutton, Brendan F Boyce, Brendan Lee
Nat Med. 2008 Mar;14(3):299-305. doi: 10.1038/nm1712. Epub 2008 Feb 24.